Articles de revues : « Mda adduct »

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Zagol-Ikapite, Irene, Iberia Romina Sosa, Audra M. Judd, Olivier Boutaud et John A. Oates. « Quantification Of Malondialdehyde Adducts In Platelet Activation As An Indicator Of Proinflammatory and Prothombotic State ». Blood 122, n^o 21 (15 novembre 2013) : 4735. http://dx.doi.org/10.1182/blood.v122.21.4735.4735.

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Background The formation of malondialdehyde (MDA) has been previously described as a product of the thromboxane synthase. However, the reported approaches for its quantification have not been reliable, stymieing its use in research. As a reactive di-carbonyl, MDA reacts with primary amines, notably lysines on proteins, to form covalent adducts of several types. Three of the products of the reaction of MDA with lysine are an N-propenal adduct, a dihydropyridine ring adduct (N-lysyl-4-methyl-2, 6-dihydropyridine-3, 5-dicarbaldehyde), and a lysyl-MDA crosslink. Measurement of platelet protein modifications, such as MDA adducts, could provide a specific marker of in vivo activation of platelets, since these modifications accumulate over the lifespan of the platelet. Methods and Results To investigate thromboxane synthase-dependent formation of MDA adducts on platelet proteins, we developed an LC/MS/MS method for analysis of one of the MDA adducts, the lysyl-MDA crosslink, employing a [13C12] labeled internal standard. We demonstrated that levels of lysyl-MDA crosslink in human platelets are increased following its activation with arachidonic acid. This increase is inhibited by aspirin, the thromboxane synthase inhibitor, ozagrel and by γ-ketoaldehyde specific scavengers: 3-Methoxysalicylamine (3-MOSA) and Salicylamine (SA). To determine whether lysyl-MDA crosslinks reflect in vivo platelet activation, we analyzed samples from patients with medical conditions known to be associated with increased platelet activation. We employed traditional methods of measuring platelet activation: flow cytometry of p-selectin and reticulated platelets, and serum thromboxane, to measure platelet activation in patients with metabolic syndrome and sickle cell disease. These assays were compared with the levels of lysyl-MDA-crosslinks. In both populations, the levels of MDA-lysine-crosslink are increased by 2.5 fold compared to healthy volunteers and provide greater discrimination between groups than p-selectin expression and reticulated platelets. The inhibition of the lysyl-MDA crosslink adduct in patients taking NSAIDs further confirms the specificity for thromboxane synthase-dependent MDA modifications on platelet proteins. Discussion The results of this study provide compelling evidence that MDA-protein adducts in platelets may be a useful marker of in vivo platelet activation in humans and potentially helpful in predicting thrombotic risk and the benefit of antiplatelet therapy in patients with medical conditions associated with platelet hyperactivity. Disclosures: No relevant conflicts of interest to declare.

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Huang, Jiansheng, Patricia G. Yancey, Huan Tao, Mark S. Borja, Loren E. Smith, Valentina Kon, Sean S. Davies et MacRae F. Linton. « Reactive Dicarbonyl Scavenging Effectively Reduces MPO-Mediated Oxidation of HDL and Restores PON1 Activity ». Nutrients 12, n^o 7 (30 juin 2020) : 1937. http://dx.doi.org/10.3390/nu12071937.

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Atheroprotective functions of high-density lipoproteins (HDL) are related to the activity of HDL-associated enzymes such as paraoxonase 1 (PON1). We examined the impact of inhibition of myeloperoxidase (MPO)-mediated HDL oxidation by PON1 on HDL malondialdehyde (MDA) content and HDL function. In the presence of PON1, crosslinking of apoAI in response to MPO-mediated oxidation of HDL was abolished, and MDA-HDL adduct levels were decreased. PON1 prevented the impaired cholesterol efflux capacity of MPO-oxidized HDL from Apoe−/− macrophages. Direct modification of HDL with MDA increased apoAI crosslinking and reduced the cholesterol efflux capacity. MDA modification of HDL reduced its anti-inflammatory function compared to native HDL. MDA-HDL also had impaired ability to increase PON1 activity. Importantly, HDL from subjects with familial hypercholesterolemia (FH-HDL) versus controls had increased MDA-apoAI adducts, and PON1 activity was also impaired in FH. Consistently, FH-HDL induced a pro-inflammatory response in Apoe−/− macrophages and had an impaired ability to promote cholesterol efflux. Interestingly, reactive dicarbonyl scavengers, including 2-hydroxybenzylamine (2-HOBA) and pentyl-pyridoxamine (PPM), effectively abolished MPO-mediated apoAI crosslinking, MDA adduct formation, and improved cholesterol efflux capacity. Treatment of hypercholesterolemic mice with reactive dicarbonyl scavengers reduced MDA-HDL adduct formation and increased HDL cholesterol efflux capacity, supporting the therapeutic potential of reactive carbonyl scavenging for improving HDL function.

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SUZUKI, DAISUKE, TOSHIO MIYATA, NOBORU SAOTOME, KATSUNORI HORIE, REIKO INAGI, YOSHINARI YASUDA, KOJI UCHIDA et al. « Immunohistochemical Evidence for an Increased Oxidative Stress and Carbonyl Modification of Proteins in Diabetic Glomerular Lesions ». Journal of the American Society of Nephrology 10, n^o 4 (avril 1999) : 822–32. http://dx.doi.org/10.1681/asn.v104822.

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Abstract. Advanced glycation end products (AGE) include a variety of protein adducts whose accumulation has been implicated in tissue damage associated with diabetic nephropathy (DN). It was recently demonstrated that among AGE, glycoxidation products, whose formation is closely linked to oxidation, such as carboxymethyllysine (CML) and pentosidine, accumulate in expanded mesangial matrix and nodular lesions in DN, in colocalization with malondialdehyde-lysine (MDA-lysine), a lipoxidation product, whereas pyrraline, another AGE structure whose deposition is rather independent from oxidative stress, was not found within diabetic glomeruli. Because CML, pentosidine, and MDA-lysine are all formed under oxidative stress by carbonyl amine chemistry between protein amino group and carbonyl compounds, their colocalization suggests a local oxidative stress and increased protein carbonyl modification in diabetic glomerular lesions. To address this hypothesis, human renal tissues from patients with DN or IgA nephropathy were examined with specific antibodies to characterize most, if not all, carbonyl modifications of proteins by autoxidation products of carbohydrates, lipids, and amino acids: CML (derived from carbohydrates, lipids, and amino acid), pentosidine (derived from carbohydrates), MDA-lysine (derived from lipids), 4-hydroxynonenal-protein adduct (derived from lipids), and acrolein-protein adduct (derived from lipids and amino acid). All of the protein adducts were identified in expanded mesangial matrix and nodular lesions in DN. In IgA nephropathy, another primary glomerular disease leading to end-stage renal failure, despite positive staining for MDA-lysine and 4-hydroxynonenal-protein adduct in the expanded mesangial area, CML, pentosidine, and acrolein-protein adduct immunoreactivities were only faint in glomeruli. These data suggest a broad derangement in nonenzymatic biochemistry in diabetic glomerular lesions, and implicate an increased local oxidative stress and carbonyl modification of proteins in diabetic glomerular tissue damage (“carbonyl stress”).

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Zucchi, Hélène, Hervé Pageon, Daniel Asselineau, Marion Ghibaudo, Inês Sequeira et Sarah Girardeau-Hubert. « Assessing the Role of Carbonyl Adducts, Particularly Malondialdehyde Adducts, in the Development of Dermis Yellowing Occurring during Skin Photoaging ». Life 12, n^o 3 (10 mars 2022) : 403. http://dx.doi.org/10.3390/life12030403.

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Solar elastosis is associated with a diffuse yellow hue of the skin. Photoaging is related to lipid peroxidation leading to the formation of carbonyl groups. Protein carbonylation can occur by addition of reactive aldehydes, such as malondialdehyde (MDA), 4-hydroxy-nonenal (4-HNE), and acrolein. All the proteins concerned with this modification, and the biological consequences of adduct formation, are not completely identified. The link between yellowish skin and dermal carbonylated proteins induced by aldehyde adducts was investigated. The study was carried out on ex vivo skin samples from sun-exposed or sun-protected areas and on in vitro dermal equivalent models incubated with 5 mM MDA, 4-HNE, or acrolein. The yellow color and the level of MDA, 4-HNE, and acrolein adducts were evaluated. Yellowish color differences were detected in the dermis of sun-exposed skin compared to sun-protected skin and in in vitro models following addition of MDA, 4-HNE, or acrolein. The yellowing was correlated with the carbonyl adducts increasing in the dermis and in in vitro models incubated with aldehydes. The stronger yellowing seemed to be mediated more by MDA than 4-HNE and acrolein. These observations suggest that dermal carbonylation especially induced by MDA result in the yellow hue of dermis and is involved, in part, in the yellowing observed during skin photoaging.

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Prasad, Ankush, Claudio Rossi, Renuka Ramalingam Manoharan, Michaela Sedlářová, Lorenzo Cangeloni, Deepak Rathi, Gabriella Tamasi, Pavel Pospíšil et Marco Consumi. « Bioactive Compounds and Their Impact on Protein Modification in Human Cells ». International Journal of Molecular Sciences 23, n^o 13 (4 juillet 2022) : 7424. http://dx.doi.org/10.3390/ijms23137424.

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Reactive oxygen species (ROS) represent a group of molecules with a signaling role that are involved in regulating human cell proliferation and differentiation. Increased ROS concentrations are often associated with the local nonspecific oxidation of biological macromolecules, especially proteins and lipids. Free radicals, in general, may randomly damage protein molecules through the formation of protein-centered radicals as intermediates that, in turn, decay into several end oxidation products. Malondialdehyde (MDA), a marker of free-radical-mediated lipid oxidation and cell membrane damage, forms adducts with proteins in a nonspecific manner, leading to the loss of their function. In our study, we utilized U-937 cells as a model system to unveil the effect of four selected bioactive compounds (chlorogenic acid, oleuropein, tomatine, and tyrosol) to reduce oxidative stress associated with adduct formation in differentiating cells. The purity of the compounds under study was confirmed by an HPLC analysis. The cellular integrity and changes in the morphology of differentiated U-937 cells were confirmed with confocal microscopy, and no significant toxicity was found in the presence of bioactive compounds. From the Western blot analysis, a reduction in the MDA adduct formation was observed in cells treated with compounds that underlaid the beneficial effects of the compounds tested.

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Carbonneau, M. A., E. Peuchant, D. Sess, P. Canioni et M. Clerc. « Free and bound malondialdehyde measured as thiobarbituric acid adduct by HPLC in serum and plasma ». Clinical Chemistry 37, n^o 8 (1 août 1991) : 1423–29. http://dx.doi.org/10.1093/clinchem/37.8.1423.

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Abstract Assay of free and total malondialdehyde (MDA) in human serum and plasma from healthy subjects and from patients with high risk of lipoperoxidation was performed as follows: (a) acidic (HClO4, pH 1, at 20 degrees C) or basic (NaOH, pH 13, at 60 degrees C) treatments for 30 min; (b) reaction of the protein-free extract (obtained by acid precipitation) with thiobarbituric acid (TBA); (c) HPLC separation on C18 columns with an eluting solution of methanol/phosphate buffer, 10 mmol/L, pH 5.8 (40/60, by vol), at a flow rate of 1.5 mL/min. Free MDA averaged 0.042 (SEM 0.008) and 0.043 (SEM 0.007) mumol/L, respectively, in serum and plasma from healthy subjects. Free (+/- SEM) MDA increased significantly in the plasma from cancer patients (0.270 +/- 0.047 mumol/L) and from hemodialyzed patients (0.214 +/- 0.035 mumol/L). In serum of hemodialyzed patients, analyses for total MDA were unsuitable because of interfering peaks. MDA bound to NH2 groups constituted 83.2% and 83.5% of total MDA in serum and plasma of healthy subjects, respectively, and only 58% in plasma of hemodialyzed patients.

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Wong, S. H., J. A. Knight, S. M. Hopfer, O. Zaharia, C. N. Leach et F. W. Sunderman. « Lipoperoxides in plasma as measured by liquid-chromatographic separation of malondialdehyde-thiobarbituric acid adduct. » Clinical Chemistry 33, n^o 2 (1 février 1987) : 214–20. http://dx.doi.org/10.1093/clinchem/33.2.214.

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Abstract This assay of plasma lipoperoxides involves hydrolysis in dilute H3PO4 at 100 degrees C; complexation of malondialdehyde (MDA), a hydrolysis product, with thiobarbituric acid (TBA); methanol precipitation of plasma proteins; fractionation of the protein-free extract on a C18 column; and spectrophotometric quantification of the MDA-TBA adduct at 532 nm. The detection limit was 0.15 mumol of MDA per liter of plasma. Run-to-run precision (CV) averaged 8 to 13%. Analytical recovery of MDA after addition of tetraethoxypropane standards to 21 specimens of human or rat plasma averaged 98% (SD 7%). Lipoperoxide concentrations (as MDA) averaged 0.60 (SD 0.13) mumol/L in plasma specimens from 41 healthy persons and 1.4 (SD 0.3) mumol/L in plasma specimens from 12 control rats. Mean lipoperoxide concentrations were 1.5 to 2.3 times as great in plasma sampled from rats one to three days after subcutaneous administration of NiCl2 at dosages (250 to 750 mumol per kilogram body wt) previously shown to induce lipid peroxidation in lung, liver, and kidney.

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Cipierre, Cécile, Stéphane Haÿs, Delphine Maucort-Boulch, Jean-Paul Steghens et Jean-Charles Picaud. « Malondialdehyde Adduct to Hemoglobin : A New Marker of Oxidative Stress Suitable for Full-Term and Preterm Neonates ». Oxidative Medicine and Cellular Longevity 2013 (2013) : 1–6. http://dx.doi.org/10.1155/2013/694014.

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Oxidative stress may play a central role in the onset of many diseases during the neonatal period. Malondialdehyde (MDA) is a marker of lipid peroxidation. The aim of this study was to evaluate a new marker, the malondialdehyde adduct to hemoglobin (MDA-Hb), which is measured in red blood cells (RBCs) and thus does not require that an additional blood sample be drawn. In this prospective study, we first adapted the measurement method previously described to Hb solutions obtained from washed RBCs and then evaluated the suitability of the method for use in neonates. MDA-Hb concentrations were measured by liquid chromatography-mass spectrometry. We compared the concentrations of MDA-Hb between preterm and term neonates. Erythrocyte samples were collected at birth from 60 healthy neonates (29 full-term and 31 preterm), as well as from 50 preterm neonates with uncomplicated postnatal evolution during the first months of life. We found a significantly higher MDA-Hb concentration at birth in preterm neonates (). During the first months of life, MDA-Hb concentrations were 9.4 nanomol/g Hb in hospitalized preterm neonates. MDA-Hb could be used to assess oxidative stress in preterm neonates. Together with clinical variables, it could be a useful marker for oxidative stress exposition in these higher risk patients.

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Cipierre, Cécile, Stéphane Haÿs, Delphine Maucort-Boulch, Jean-Paul Steghens et Jean-Charles Picaud. « Adduct of Malondialdehyde to Hemoglobin : A New Marker of Oxidative Stress That Is Associated with Significant Morbidity in Preterm Infants ». Oxidative Medicine and Cellular Longevity 2013 (2013) : 1–8. http://dx.doi.org/10.1155/2013/901253.

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Preterm infants (PT) are particularly exposed to oxidative stress (OS), and a blood-sparing marker, the malondialdehyde adduct to hemoglobin (MDA-Hb), may be useful to accurately assess OS-related neonatal morbidity. In a prospective study, MDA-Hb concentrations were assessed in two groups of PT, one with and one without severe neonatal morbidity as estimated by a composite index of severe morbidity (ISM). All PT born in a single tertiary care NICU (<32 weeks and birth weight<1500 g) were consecutively included. MDA-Hb and blood glutathione (GSH) concentrations were measured by liquid chromatography-mass spectrometry during the first 6 weeks of life. Linear regressions and a multilevel model were fitted to study the relationship between MDA-Hb or GSH and ISM. Of the 83 PT (mean ± SD:28.3±2weeks,1089±288 g), 21% presented severe neonatal morbidity. In the multivariate model, MDA-Hb concentrations were significantly higher in the ISM+ group than in the ISM– group during the first 6 weeks of life (P=0.009). No significant difference in GSH concentrations was observed between groups (P=0.180). MDA-Hb is a marker of interest for estimating oxidative stress in PT and could be useful to evaluate the impact of strategies to improve perinatal outcomes.

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Knight, J. A., L. McClellan et J. K. Staheli. « Cerebrospinal fluid lipoperoxides quantified by liquid chromatography, and determination of reference values ». Clinical Chemistry 36, n^o 1 (1 janvier 1990) : 139–42. http://dx.doi.org/10.1093/clinchem/36.1.139.

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Abstract Cerebrospinal fluid lipoperoxides, measured as the malondialdehyde-thiobarbituric acid (MDA-TBA) adduct, were quantified by adapting the plasma liquid-chromatographic method of Wong et al. (Clin Chem 1987;33:214-20) to cerebrospinal fluid. Reference values for spinal fluid specimens from 91 adults, ages 17 to 95 y, and 37 children, ages 8 d to 8 y, were determined. Their concentrations were not significantly different (P = 0.222), adults having a mean (and SD) of 0.11 (0.06) mumol and children 0.10 (0.04) mumol of MDA per liter. Their ranges were 0.02-0.26 and 0.04-0.21 mumol of MDA per liter, respectively. We found concentrations in cerebrospinal fluid to be increased in several central nervous system disorders, including seizures, cerebral infarction, alcoholic encephalopathy, and, perhaps, prematurity. The presence of other thiobarbituric acid-reactive substances in cerebrospinal fluid stresses the importance of using highly specific techniques when lipoperoxides are measured in body fluids.

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Anane, R., et E. E. Creppy. « Lipid peroxidation as pathway of aluminium cytotoxicity in human skin fibroblast cultures : Prevention by superoxide dismutase+catalase and vitamins E and C ». Human & ; Experimental Toxicology 20, n^o 9 (septembre 2001) : 477–81. http://dx.doi.org/10.1191/096032701682693053.

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Lipid peroxidation is one of the main manifestations of oxidative damage and has been found to play an important role in the toxicity and carcinogenicity of many xenobiotics. In the present study, we investigated the possible induction of lipid peroxidation by aluminium in human foreskin fibroblast cultures by assaying the malondialde hyde (MDA) produced inside the cells. The MDA–thiobarbituric acid (TBA) adduct was assayed by HPLC using fluorometric quantification after extraction in n-butanol. Lactate dehydrogenase (LDH) release was used as a marker of aluminium toxicity. MDA production was significantly increased after 24 h incubation with aluminium and paralleled LDH release. Superoxide dismutase (SOD)+catalase and vitamins C and E added in the culture medium as oxygen radical and free radical scavengers were efficient in preventing MDA production by aluminium, indicating that oxidative processes are one of the main pathways whereby this metal induces cytotoxicity. The latter is also largely prevented, thus confirming the link between oxidative stress induced by aluminium and its cytotoxicity in human skin fibroblasts. Human & Experimental Toxicology (2001) 20, 477–481.

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Qin, Liyun, Maria Guitart, Víctor Curull, Albert Sánchez-Font, Xavier Duran, Jun Tang, Mireia Admetlló et Esther Barreiro. « Systemic Profiles of microRNAs, Redox Balance, and Inflammation in Lung Cancer Patients : Influence of COPD ». Biomedicines 9, n^o 10 (29 septembre 2021) : 1347. http://dx.doi.org/10.3390/biomedicines9101347.

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Lung cancer (LC) risk increases in patients with chronic respiratory diseases (COPD). MicroRNAs and redox imbalance are involved in lung tumorigenesis in COPD patients. Whether systemic alterations of those events may also take place in LC patients remains unknown. Our objectives were to assess the plasma levels of microRNAs, redox balance, and cytokines in LC patients with/without COPD. MicroRNAs (RT-PCR) involved in LC, oxidized DNA, MDA-protein adducts, GSH, TEAC, VEGF, and TGF-beta (ELISA) were quantified in plasma samples from non-LC controls (n = 45), LC-only patients (n = 32), and LC-COPD patients (n = 91). In LC-COPD patients compared to controls and LC-only, MDA-protein adduct levels increased, while those of GSH decreased, and two patterns of plasma microRNA were detected. In both LC patient groups, miR-451 expression was downregulated, while those of microRNA-let7c were upregulated, and levels of TEAC and TGF-beta increased compared to the controls. Correlations were found between clinical and biological variables. A differential expression profile of microRNAs was detected in patients with LC. Moreover, in LC patients with COPD, plasma oxidative stress levels increased, whereas those of GSH declined. Systemic oxidative and antioxidant markers are differentially expressed in LC patients with respiratory diseases, thus implying its contribution to the pathogenesis of tumorigenesis in these patients.

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Bremer, C., B. U. Bradford, K. J. Hunt, K. T. Knecht, H. D. Connor, R. P. Mason et R. G. Thurman. « Role of Kupffer cells in the pathogenesis of hepatic reperfusion injury ». American Journal of Physiology-Gastrointestinal and Liver Physiology 267, n^o 4 (1 octobre 1994) : G630—G636. http://dx.doi.org/10.1152/ajpgi.1994.267.4.g630.

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The purpose of this study was to evaluate the role of Kupffer cell activation in the pathogenesis of reperfusion injury. In a blood-free liver perfusion model, pericentral hypoxia and reperfusion injury occurred. Lactate dehydrogenase (LDH) and malondialdehyde (MDA) release, oxygen uptake, and trypan blue staining were assessed. Within the first 10 min of reflow, LDH and MDA release reached maximal values of 44 U.g-1.h-1 and 115 nmol.g-1.h-1, respectively. Trypan blue cell staining was confined to pericentral regions of the liver lobule. When Kupffer cells were inactivated with GdCl3, release of enzymes and MDA was reduced significantly by > 50%, and hepatic cell death was almost completely absent. Since increases in MDA suggested involvement of free radicals, livers were perfused with phenyl N-t-butylnitrone (5 mM), a spin-trapping agent. Analysis of liver tissue by electron paramagnetic resonance spectroscopy revealed a typical six-line spectrum, providing direct evidence that carbon-centered radicals were generated on reflow. GdCl3 treatment decreased radical adduct formation by approximately 50%. Collectively, these results strongly support the hypothesis that activation of Kupffer cells plays an important role in the pathogenesis of hepatic reperfusion injury.

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Duryee, Michael J., Lynell W. Klassen, Courtney S. Schaffert, Dean J. Tuma, Carlos D. Hunter, Robert P. Garvin, Daniel R. Anderson et Geoffrey M. Thiele. « Malondialdehyde–acetaldehyde adduct is the dominant epitope after MDA modification of proteins in atherosclerosis ». Free Radical Biology and Medicine 49, n^o 10 (novembre 2010) : 1480–86. http://dx.doi.org/10.1016/j.freeradbiomed.2010.08.001.

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Minoda, Yuko, et Evan D. Kharasch. « Halothane-dependent Lipid Peroxidation in Human Liver Microsomes Is Catalyzed by Cytochrome P4502A6 (CYP2A6) ». Anesthesiology 95, n^o 2 (1 août 2001) : 509–14. http://dx.doi.org/10.1097/00000542-200108000-00037.

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Background Halothane is extensively (approximately 50%) metabolized in humans and undergoes both oxidative and reductive cytochrome P450-catalyzed hepatic biotransformation. Halothane is reduced under low oxygen tensions by CYP2A6 and CYP3A4 in human liver microsome to an unstable free radical, and then to the volatile metabolites chlorodifluoroethene (CDE) and chlorotrifluoroethane (CTE). The free radical is also thought to initiate lipid peroxidation. Halothane-dependent lipid peroxidation has been shown in animals in vitro and in vivo but has not been evaluated in humans. This investigation tested the hypothesis that halothane causes lipid peroxidation in human liver microsomes, identified P450 isoforms responsible for halothane-dependent lipid peroxidation, and tested the hypothesis that lipid peroxidation is prevented by inhibiting halothane reduction. Methods Halothane metabolism was determined using human liver microsomes or cDNA-expressed P450. Lipid peroxidation was quantified by malondialdehyde (MDA) formation using high-pressure liquid chromatography-ultraviolet analysis of the thiobarbituric acid-MDA adduct. CTE and CDE were determined by gas chromatography-mass spectrometry. Results Halothane caused MDA formation in human liver microsomes at rates much lower than in rat liver microsomes. Human liver microsomal MDA production exhibited biphasic enzyme kinetics, similar to CDE and CTE production. MDA production was inhibited by the CYP2A6 inhibitor methoxsalen but not by the CYP3A4 inhibitor troleandomycin. Halothane-dependent MDA production was catalyzed by cDNA-expressed CYP2A6 but not CYP3A4 or P450 reductase alone. CYP2A6-catalyzed MDA production was inhibited by methoxsalen or anti-CYP2A6 antibody. Conclusions Halothane causes lipid peroxidation in human liver microsomes, which is catalyzed by CYP2A6, and inhibition of halothane reduction prevents halothane-dependent lipid peroxidation in vitro.

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Knaś, M., M. Maciejczyk, I. Daniszewska, A. Klimiuk, J. Matczuk, U. Kołodziej, D. Waszkiel, J. R. Ładny, M. Żendzian-Piotrowska et A. Zalewska. « Oxidative Damage to the Salivary Glands of Rats with Streptozotocin-Induced Diabetes-Temporal Study : Oxidative Stress and Diabetic Salivary Glands ». Journal of Diabetes Research 2016 (2016) : 1–13. http://dx.doi.org/10.1155/2016/4583742.

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Objective.This study evaluated oxidative damage caused to the salivary glands in streptozotocin-induced diabetes (DM).Materials and Methods.Rats were divided into 4 groups: groups 1 and 2, control rats, and groups 3 and 4, DM rats. 8-Hydroxy-2′-deoxyguanosine (8-OHdG), protein carbonyl (PC), 4-hydroxynonenal protein adduct (4-HNE), oxidized and/or MDA-modified LDL-cholesterol (oxy-LDL/MDA), 8-isoprostanes (8-isoP), and oxidative stress index (OSI) were measured at 7 (groups 1 and 3) and 14 (groups 2 and 4) days of experiment.Results.The unstimulated salivary flow in DM rats was reduced in the 2nd week, while the stimulated flow was decreased throughout the duration of the experiment versus control. OSI was elevated in both diabetic glands in the 1st and 2nd week, whereas 8-isoP and 8-OHdG were higher only in the parotid gland in the second week. PC and 4-HNE were increased in the 1st and 2nd week, whereas oxy-LDL/MDA was increased in the 2nd week in the diabetic parotid glands.Conclusions.Diabetes induces oxidative damage of the salivary glands, which seems to be caused by processes taking place in the salivary glands, independently of general oxidative stress. The parotid glands are more vulnerable to oxidative damage in these conditions.

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Frescas, David, Christelle M. Roux, Semra Aygun-Sunar, Anatoli S. Gleiberman, Peter Krasnov, Oleg V. Kurnasov, Evguenia Strom et al. « Senescent cells expose and secrete an oxidized form of membrane-bound vimentin as revealed by a natural polyreactive antibody ». Proceedings of the National Academy of Sciences 114, n^o 9 (13 février 2017) : E1668—E1677. http://dx.doi.org/10.1073/pnas.1614661114.

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Studying the phenomenon of cellular senescence has been hindered by the lack of senescence-specific markers. As such, detection of proteins informally associated with senescence accompanies the use of senescence-associated β-galactosidase as a collection of semiselective markers to monitor the presence of senescent cells. To identify novel biomarkers of senescence, we immunized BALB/c mice with senescent mouse lung fibroblasts and screened for antibodies that recognized senescence-associated cell-surface antigens by FACS analysis and a newly developed cell-based ELISA. The majority of antibodies that we isolated, cloned, and sequenced belonged to the IgM isotype of the innate immune system. In-depth characterization of one of these monoclonal, polyreactive natural antibodies, the IgM clone 9H4, revealed its ability to recognize the intermediate filament vimentin. By using 9H4, we observed that senescent primary human fibroblasts express vimentin on their cell surface, and MS analysis revealed a posttranslational modification on cysteine 328 (C328) by the oxidative adduct malondialdehyde (MDA). Moreover, elevated levels of secreted MDA-modified vimentin were detected in the plasma of aged senescence-accelerated mouse prone 8 mice, which are known to have deregulated reactive oxygen species metabolism and accelerated aging. Based on these findings, we hypothesize that humoral innate immunity may recognize senescent cells by the presence of membrane-bound MDA-vimentin, presumably as part of a senescence eradication mechanism that may become impaired with age and result in senescent cell accumulation.

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Hesaruiyeh, Farzaneh Allahdinian, Saeed Rajabi, Mohadeseh Motamed-Jahromi, Mohammad Sarhadi, Michelle L. Bell, Razieh Khaksefidi, Somayeh Sarhadi et al. « A Pilot Study on the Association of Lead, 8-Hydroxyguanine, and Malondialdehyde Levels in Opium Addicts’ Blood Serum with Illicit Drug Use and Non-Addict Persons ». International Journal of Environmental Research and Public Health 19, n^o 15 (26 juillet 2022) : 9110. http://dx.doi.org/10.3390/ijerph19159110.

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While a large body of literature has shown the health problems of illicit drug use, research is needed on how substance abuse impacts DNA damage and contaminants in blood, especially given Pb-contaminated opium. This pilot study aimed to evaluate the levels of lead (Pb), 8-hydroxy di-guanine (8-oxo-Gua), and malondialdehyde (MDA) in the blood serum of opium addicts and non-addict people. The current study is a case–control study with a cross-sectional design. A sample of 50 opium-addicted and non-addict adults were chosen for this study using convenience and random sampling methods. Participants were divided into two groups: addicts and non-addicts. The atomic absorption spectroscopy method was used to measure the quantity of Pb, and the Enzyme-Linked Immunosorbent Assay (ELISA) method was used to measure the amount of 8-oxo-Gua and MDA. The data were analyzed using an independent t-test. The results show that the amount of Pb in the blood serum of addicted women and men was higher than levels in non-addict men and women, for the study participants (p-value = 0.001). Blood levels were not significantly different between addicts and non-addicts for men or women for 8-oxo-Gua (p-value = 0.647 for women and p-value = 0.785 for men) and MDA (p-value = 0.867 for women and p-value = 0.995 for men). In general, addicts’ blood Pb levels were found to be substantially higher than those of normal non-addict persons in this pilot study. As a result, testing for blood Pb levels in addicts may be informative in instances when symptoms are inconclusive.

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Leong, Chee Onn, Marie Suggitt, David J. Swaine, Michael C. Bibby, Malcolm F. G. Stevens et Tracey D. Bradshaw. « In vitro, in vivo, and in silico analyses of the antitumor activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazoles ». Molecular Cancer Therapeutics 3, n^o 12 (1 décembre 2004) : 1565–75. http://dx.doi.org/10.1158/1535-7163.1565.3.12.

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Abstract Phortress is a novel, potent, and selective experimental antitumor agent. Its mechanism of action involves induction of CYP1A1-catalyzed biotransformation of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) to generate electrophilic species, which covalently bind to DNA, exacting lethal damage to sensitive tumor cells, in vitro and in vivo. Herein, we investigate the effects of DNA adduct formation on cellular DNA integrity and progression through cell cycle and examine whether a relevant pharmacodynamic end point may be exploited to probe the clinical mechanism of action of Phortress and predict tumor response. Single cell gel electrophoresis (SCGE) was applied to quantify DNA damage and cell cycle analyses conducted upon 5F 203 treatment of benzothiazole-sensitive MCF-7 and inherently resistant MDA-MB-435 breast carcinoma cells. Following treatment of xenograft-bearing mice and mice possessing hollow fiber implants containing MCF-7 or MDA-MB-435 cells with Phortress (20 mg/kg, i.p., 24 hours), tumor cells and xenografts were recovered for analyses by SCGE. Dose- and time-dependent DNA single and double strand breaks occurred exclusively in sensitive cells following treatment with 5F 203 in vitro (10 nmol/L–10 μmol/L; 24–72 hours). In vivo, Phortress-sensitive and Phortress-resistant tumor cells were distinct; moreover, DNA damage in xenografts, following treatment of mice with Phortress, could be determined. Interrogation of the mechanism of action of 5F 203 in silico by self-organizing map-based cluster analyses revealed modulation of phosphatases and kinases associated with cell cycle regulation, corroborating observations of selective cell cycle perturbation by 5F 203 in sensitive cells. By conducting SCGE, tumor sensitivity to Phortress, an agent currently undergoing clinical evaluation, may be determined.

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Shahid, Amina, Anoosh Qayyum, Khalida Anwar, Nusrat Tariq, Sultan Ahmad, Naveed Shuja, Sara Zahid, Sulayman Waquar et Arif Malik. « Expression of Prophetic Variables of Analytical Importance and their Potential Role in Breast Cancer Patient Underwent Surgical Procedure ». Pakistan Journal of Medical and Health Sciences 16, n^o 9 (30 septembre 2022) : 925–27. http://dx.doi.org/10.53350/pjmhs22169925.

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Objective: Study the role of prophetic variables and their role in breast cancer patients especially those underwent surgical procedures. Study Design: Cross-sectional study Place and Duration: Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore. Martials and Methods: Twenty diagnosed patients of breast cancer facing surgical procedure were selected from the surgical department, Jinnah hospital, Lahore and twenty normal females were included in the study. Complete blood count (CBC) of the selected individuals was performed. Other biochemical markers Malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), 4-Hydroxynonenol (4-HNE), Isoprostanes F2α (IsoP- F2α), Interleukin-6 (IL-6), Matrix metalloproteinases-9 (MMP-9), Tumor Necrosis factor-alpha (TNF-α), Prostaglindin-E2 (PGE-2) were measured by commercially available kits. Results: The mean weight, BMI, WBCs, platelet count, lymphocyte and neutrophil value were higher in patients compared to the controls with statistically significant differences (p< 0.05). However, the mean MDA, 8-OHdG, 4-HNE, Iso-P2α, IL-6, MMP-9, TNF-α and PGE-2 value significantly higher than the control subjects (p < 0.05). Conclusion: Findings of the study demonstrated the significant role of the said prophetic variables that were having their medicinal importance in the invagination of breast cancer among the patients undergone surgical interventions. It shows the significant increases in the levels of discussed markers that show increased oxidative stress leading to cell damage that can be observed within the studied group. Therefore, early investigation of the said variables and ruling out the true causes could help in addressing the oncological complications that one undergoes after being through the surgical interventions and in providing the best possible treatments Keywords: Epidermal growth factor receptor, metastatic invasion, breast cancer surgery, matrix metalloproteinase, DNA adduct

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Duryee, Michael J., Dahn L. Clemens, Patrick J. Opperman, Geoffrey M. Thiele, Logan M. Duryee, Robert P. Garvin et Daniel R. Anderson. « Malondialdehyde-Acetaldehyde Modified (MAA) Proteins Differentially Effect the Inflammatory Response in Macrophage, Endothelial Cells and Animal Models of Cardiovascular Disease ». International Journal of Molecular Sciences 22, n^o 23 (30 novembre 2021) : 12948. http://dx.doi.org/10.3390/ijms222312948.

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Chronic inflammation plays a critical role in the pathogenesis of atherosclerosis. Currently, the mechanism(s) by which inflammation contributes to this disease are not entirely understood. Inflammation is known to induce oxidative stress, which can lead to lipid peroxidation. Lipid peroxidation can result in the production of reactive by-products that can oxidatively modify macromolecules including DNA, proteins, and lipoproteins. A major reactive by-product of lipid peroxidation is malondialdehyde (MDA). MDA can subsequently break down to form acetaldehyde (AA). These two aldehydes can covalently interact with the epsilon (ε)-amino group of lysines within proteins and lipoproteins leading to the formation of extremely stable, highly immunogenic malondialdehyde/acetaldehyde adducts (MAA-adducts). The aim of this study was to investigate the inflammatory response to MAA-modified human serum albumin (HSA-MAA) and low-density lipoprotein (LDL-MAA). We found that animals injected with LDL-MAA generate antibodies specific to MAA-adducts. The level of anti-MAA antibodies were further increased in an animal model of atherosclerosis fed a Western diet. An animal model that combined both high fat diet and immunization of MAA-modified protein resulted in a dramatic increase in antibodies to MAA-adducts and vascular fat accumulation compared with controls. In vitro exposure of endothelial cells and macrophages to MAA-modified proteins resulted in increased fat accumulation as well as increased expression of adhesion molecules and pro-inflammatory cytokines. The expression of cytokines varied between the different cell lines and was unique to the individual modified proteins. The results of these studies demonstrate that different MAA-modified proteins elicit unique responses in different cell types. Additionally, the presence of MAA-modified proteins appears to modulate cellular metabolism leading to increased accumulation of triglycerides and further progression of the inflammatory response.

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Abd-Allah, Adel R. A., Gouda K. Helal, Abdulaziz A. Al-Yahya, Abdulaziz M. Aleisa, Salim S. Al-Rejaie et Saleh A. Al-Bakheet. « Pro-Inflammatory and Oxidative Stress Pathways which Compromise Sperm Motility and Survival May Be Altered by L-Carnitine ». Oxidative Medicine and Cellular Longevity 2, n^o 2 (2009) : 73–81. http://dx.doi.org/10.4161/oxim.2.2.8177.

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The testis is an immunologically privileged organ. Sertoli cells can form a blood-testis barrier and protect sperm cells from self-immune system attacks. Spermatogenesis may be inhibited by severe illness, bacterial infections and chronic inflammatory diseases but the mechanism(s) is poorly understood. Our objective is to help in understanding such mechanism(s) to develop protective agents against temporary or permanent testicular dysfunction. Lipopolysaccaride (LPS) is used as a model of animal sepsis while L-carnitine (LCR) is used as a protective agent. A total of 60 male Swiss albino rats were divided into four groups (15/group). The control group received Saline; the 2ndgroup was given LCR (500 mg/kg i.p, once). The third group was treated with LPS (5 mg/kg i.p once) and the fourth group received LCR then LPS after three hours. From each group, five rats were used for histopathological examination. Biochemical parameters were assessed in the remaining ten rats. At the end of the experiment, animals were lightly anaesthetized with ether where blood samples were collected and testes were dissected on ice. Sperm count and motility were evaluated from cauda epididymis in each animal. Also, oxidative stress was evaluated by measuring testicular contents of reduced glutathione (GSH), malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-HDG, the DNA adduct for oxidative damage) in testicular DNA. The pro-inflammatory mediator nitric oxide (NO) in addition to lactate dehydrogenase (LDHx) isoenzyme-x activity as an indicator for normal spermatozoal metabolism were assessed in testicular homogenate. Serum interlukin (IL)-2 level was also assessed as a marker for T-helper cell function. The obtained data revealed that LPS induced marked reductions in sperm's count and motility, obstruction in seminiferous tubules, hypospermia and dilated congested blood vessels in testicular sections concomitant with decreased testicular GSH content and LDHx activity. Moreover, the testicular levels of MDA, 8-HDG (in testicular DNA) and NO as well as serum IL-2 level were increased. Administration of LCR before LPS returned both sperm count and motility to normal levels. Also, contents of testicular GSH, MDA, 8-HDG and NO returned back to the corresponding control values. In addition, serum IL-2 level as well as histological abnormalities were markedly improved in LCR + LPS-treated rats. In conclusion, LPS increased proinflammatory and oxidative stress markers in the testis leading to a marked testicular dysfunction. L-carnitine administration ameliorates these effects by antioxidant and/or anti-inflammatory mechanisms suggesting a protective role against male infertility in severely infected or septic patients.

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Sauce, Rafael, Claudinéia Aparecida Sales de Oliveira Pinto, Carmen Ayala-Jara, Zulita Adriana Prieto, Maria Valéria Robles Velasco et André Rolim Baby. « Preliminary Protocol Development of a HPLC-TBARS-EVSC (Ex Vivo Stratum Corneum) Assay for Skin Research : Application in a Sunscreen System ». Scientia Pharmaceutica 89, n^o 2 (27 avril 2021) : 17. http://dx.doi.org/10.3390/scipharm89020017.

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Considering the importance of the cutaneous tissue investigation and the need for the development of new protocols to non-invasively establish the safety and efficacy of dermocosmetics and topical products, we aimed at developing an HPLC-TBARS-EVSC (high performance liquid chromatography–thiobarbituric acid reactive species–ex vivo stratum corneum) assay for the lipid peroxidation measurement on subjects’ stratum corneum (SC) obtained by tape stripping; additionally, we applied the HPLC-TBARS-EVSC assay in an emulsified sunscreen system containing ethylhexyl triazone and bemotrizinol as UV filters. HPLC analysis was performed in isocratic mode with 35% methanol/65% phosphate buffer (pH 7.0) as the mobile phase. The diode detector was set at 532 nm to quantify the malondialdehyde (MDA)-TBA adduct. An ex vivo tape stripping method was applied in 10 volunteers in three pre-defined regions of the volar forearms: the control; the irradiated; and the site containing the sunscreen (2.0 mg·cm−2). Ten adhesive tapes per region were used for SC removal. An exclusive ex vivo protocol to measure SC lipid peroxidation was preliminarily developed with linearity and selectivity. The protocol suggested the use of an artificial irradiation dose (5506 KJ·m−2) to improve the assay response from the SC. The sunscreen system had a significative decrease in SC lipoperoxidative damage compared to the control. Our protocol can aid in the efficacy establishment of anti-UV and antioxidant agents, for instance, in studies that aim at elucidating the level of SC lipid peroxidation and even in carrying out baseline investigations characterizing different ethnicities and genders.

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Egbuonu, Anthony Cemaluk Chinedum, Emmanuel Obi, Chinedu P. Nwuke, Cynthia Uchechi Simon, Justina Utodinachi Oleghibe, Nnaemeka Raymond Ezenwafor et Ebere Mercy Chukwu. « Monosodium Glutamate Plus Artemether-lumefantrine Overdose Altered Malondialdehyde, Total Protein and Albumin Concentration in Rats ». Advanced Journal of Graduate Research 7, n^o 1 (7 décembre 2019) : 70–79. http://dx.doi.org/10.21467/ajgr.7.1.70-79.

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This study aimed at assessing alterations in malondialdehyde, MDA, total protein and albumin concentration in the serum and liver homogenate of monosodium glutamate (MSG)-challenged rats co-treated with artemether-lumefantrine, AL. Methods involving colourimetric estimation were employed in thirty rats randomly grouped into six (n = 5) and for seven consecutive days, fed feed and water (Group A), AL therapeutic dose (Group B), AL overdose (therapeutic dose × 5) (Group C), MSG (8000 mg/kg body weight) (Group D), AL therapeutic dose plus MSG (Group E) or AL overdose plus MSG (Group F). Total protein concentration (2.64±0.09 g/dL, 2.81±0.14g/dL, respectively) in the liver homogenate of rats exposed to MSG (group D) or MSG plus AL overdose (group F) and malondialdehyde concentration in the liver homogenate of MSG plus AL overdose-fed rats (0.45±0.04 mg/ml) lowered (P<0.05) as against other groups. However, serum albumin concentration in MSG (2.59±0.13 g/dl) or AL overdose plus MSG (3.24±0.12 g/dl) fed rats was higher (P<0.05) compared to the control (2.02±0.04 g/dl). The Total protein: Albumin ratio lowered while the Albumin: total protein ratio increased in rats in MSG, AL overdose plus MSG or AL overdose groups compared with the control. Thus, the apparent MSG plus AL overdose-induced adverse influence on the studied parameters and samples of non-malarial infested rats could be via compromised liver-mediated protein metabolism capacity and bio-functions following possibly enhanced protein-malondialdehyde adduct formation in the rats.

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Gaisberger, Birgit, et Sonja Solar. « Demethoxylation and hydroxylation of methoxy- and hydroxybenzoic acids by OH-radicals. Processes of potential importance for food irradiation ». Canadian Journal of Chemistry 79, n^o 4 (1 avril 2001) : 394–404. http://dx.doi.org/10.1139/v01-058.

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The hydroxylation process for methoxy- and hydroxy-benzoic acids (MBA, HBA) induced by γ-radiation is compared. 2-, 3-, and 4-methoxybenzoic acid as well as 3-hydroxybenzoic acid have been irradiated in N2O and aerated solutions up to 1.5 kGy. The products were analyzed by HPLC. The results for 2- and 4-HBA have been taken from literature data. The OH·-adduct distribution is generally the same for the hydroxy- as well as for the methoxy-benzoic acid isomers. With both 4-HBA and 4-MBA more than 65% C3-adducts and about 15% C4-adducts are formed, which could be proved by their reactions with K3Fe(CN)6. Oxidation of the nonipso-adducts of 3-HBA and 3-MBA results in 84 and 87% of the corresponding phenols. Whereas in N2O-saturated solutions only part of the OH·-radicals leads to substrate decomposition, in the presence of air, the degradation of both kinds of compounds is equivalent to [OH·]. The nonipso OH·-adducts of the HBAs are converted into 6877% hydroxylation products. With the MBAs, the hydroxylation process is [Formula: see text] 10%. This is attributed to different decay pathways of the peroxyl radicals, intermediates formed by O2 addition to the OH·-adducts. The hydroxyperoxycyclohexadienyl radicals of the HBAs decay mainly by HO2· elimination to the corresponding phenols, those of the MBAs decay predominantly by fragmentation of the benzene ring, yielding to nonidentified aliphatic products. The replacement of -OCH3 by -OH is practically not influenced by the presence of oxygen, it increases in the sequence 3-MBA < 4-MBA < 2-MBA. For 2-MBA, yields of more than 15% are obtained. Both processes, hydroxylation as well as demethoxylation, might be of importance for the recognition of radiolytical changes in foodstuff.Key words: γ-radiolysis, methoxybenzoic acids, hydroxybenzoic acids, phenolic acids, food components, reaction mechanisms, product analysis, HPLC analysis.

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Sakuraba, K., A. Krishnamurthy, A. Circiumaru, M. Sun, V. Joshua, M. Engström, X. Zheng et al. « SAT0017 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT ». Annals of the Rheumatic Diseases 79, Suppl 1 (juin 2020) : 938.2–939. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5013.

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Background:Malondialdehyde (MDA) is a highly reactive compound produced by lipid-peroxidation in situations associated with oxidative stress. MDA can irreversibly modify proteins residues such as lysine, arginine and histidine. In addition, MDA adducts can further react with acetaldehyde to generate malondialdehyde-acetaldehyde (MAA) modifications. Such modifications can give rise to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1) and systemic lupus erythematosus (2). Recently, we have shown that anti-MDA/MAA IgG antibodies are able to promote osteoclast (OC) differentiationin vitro(1).Objectives:To investigate the molecular mechanisms triggered by anti-MDA/MAA autoantibodies during osteoclastogenesis.Methods:OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. The development of OCs was monitored by light microscopy following tartrate-resistant acid phosphatase (TRAP) staining and erosion area on synthetic calcium phosphate-coated plates. Three different recombinant human monoclonal anti-MDA/MAA antibodies, cloned from single synovial B cells of RA patients, control antibodies and Fab fragments of the antibodies were added to OC cultures. Glycolysis was inhibited by 2-deoxyglucose, and Fc-gamma receptor I or II by anti-CD64 or anti-CD16 neutralizing antibodies. IL-8 levels were measured by enzyme linked immunosorbent assay. Cellular metabolism was monitored using Seahorse XF Analyzer (extracellular acidification rate and oxygen consumption) and a colorimetric L-Lactate assay.Results:Lactic acid production correlated with the osteoclastogenetic effect of some but not all anti-MDA/MAA antibodies on OCs (R=0.4758, p=0.0252) suggesting an antibody-mediated regulation of glycolysis. Further, extracellular acidification (ECAR) and oxygen consumption (OCR) rate of the developing OCs were increased by the osteoclastogenic anti-MDA/MAA clones (maximum increase of 54% for the ECAR and 78% for the OCR by clone 146+:01G07, and maximum increase of 28% for the ECAR and 39% for the OCR by clone 1103:01H05), but not by the non-osteoclastogenetic anti-MDA/MAA clones or control antibodies. The glycolysis inhibitor 2-deoxyglucose completely abolished the osteoclastogenetic effect of the anti-MDA/MAA clones at drug concentrations that did not influenced baseline OC development. Fab2 fragments of the osteocalstogenetic anti-MDA/MAA clones had no effect on OC development and metabolism. In accordance with this, Fc-gamma receptor I neutralizing antibodies completely abolished the osteocalstogenetic effect of the anti-MDA/MAA clones. The osteoclastogenetic effect of the anti-MDA/MAA antibodies was independent of IL-8 production. In contrast to anti MDA/MAA antibodies, ACPA-mediated osteoclastogenesis was independent of glycolysis and Fc-gamma receptors but dependent on IL-8.Conclusion:Our results describe a novel glycolysis-dependent mechanism by which anti-MDA/MAA antibodies promote osteoclast development that is different from the one previously described for ACPA.References:[1] C. Grönwall et al. Journal of Autoimmunity 84 (2017) 29-45.[2] C. Wang et al. Arthritis and Rheumatism 62 (2010) 2064-2072Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Meng Sun: None declared, Vijay Joshua: None declared, Marianne Engström: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: VM has had research grants from Janssen Pharmaceutica, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina: None declared

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REQUENA, Jesús R., Min Xin FU, Mahtab U. AHMED, Alicia J. JENKINS, Timothy J. LYONS, John W. BAYNES et Suzanne R. THORPE. « Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein ». Biochemical Journal 322, n^o 1 (15 février 1997) : 317–25. http://dx.doi.org/10.1042/bj3220317.

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Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(Nε-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(Nε-lysino)propane (LML)] and lysine-HNE [3-(Nε-lysino)-4-hydroxynonan-1-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70Ő80% of total lysine loss during the reaction with MDA. LM and LML (0.002Ő0.12mmol/mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo.

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Duryee, Michael J., Benjamin M. Wiese, Jordan R. Bowman, Jared D. Vanlandingham, Lynell W. Klassen, Geoffrey E. Thiele, Carlos D. Hunter, Daniel R. Anderson, Ted R. Mikuls et Geoffrey M. Thiele. « Liver tissue metabolically transformed by alcohol induces immune recognition of liver self-proteins but not in vivo inflammation ». American Journal of Physiology-Gastrointestinal and Liver Physiology 314, n^o 3 (1 mars 2018) : G418—G430. http://dx.doi.org/10.1152/ajpgi.00183.2017.

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Precision-cut liver slices (PCLSs) provide a novel model for studies of alcoholic liver disease (ALD). This is relevant, as in vivo ethanol exposure does not appear to generate significant liver damage in ethanol-fed mice, except in the National Institute on Alcohol Abuse and Alcoholism binge model of ALD. Previous studies have shown that the two metabolites of ethanol consumption, malondialdhyde (MDA) and acetaldehyde (AA), combine to form MDA-AA (MAA) adducts, which have been correlated with the development and progression of ALD. In this study, murine PCLSs were incubated with ethanol and examined for the production of MAA adducts. PCLSs were homogenized, and homogenates were injected into C57BL/6 mice. PCLSs from control-, pair-, and ethanol-fed animals served as targets in in situ cytotoxic assays using primed T cells from mice hyperimmunized with control or ethanol-exposed PCLS homogenates. A CD45.1/CD45.2 passive-transfer model was used to determine whether T cells from the spleens of mice hyperimmunized with PCLS ethanol-exposed homogenates trafficked to the liver. PCLSs incubated with ethanol generated MAA-modified proteins in situ. Cytotoxic (CD8+) T cells from immunized mice killed naïve PCLSs from control- and pair-fed mice in vitro, a response that was blunted in PCLSs from ethanol-fed mice. Furthermore, CD45.1 CD8+ T cells from hyperimmunized mice trafficked to the liver but did not initiate liver damage. This study demonstrates that exposure to liver tissue damaged by ethanol mediates robust immune responses to well-characterized alcohol metabolites and native liver proteins in vitro. Moreover, although these proinflammatory T cells traffic to the liver, these responses appear to be dampened in vivo by locally acting pathways. NEW & NOTEWORTHY This study shows that the metabolites of ethanol and lipid breakdown produce malondialdehyde-acetaldehyde adducts in the precision-cut liver slice model system. Additionally, precision-cut liver slices exposed to ethanol and harboring malondialdehyde-acetaldehyde adducts generate liver-specific antibody and T cell responses in the spleens of naïve mice that could traffic to the liver.

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Sakuraba, K., A. Krishnamurthy, A. Circiumaru, V. Joshua, H. Wähämaa, M. Engström, M. Sun et al. « POS0400 METABOLIC CHANGES INDUCED BY ANTI-MALONDIALDEHYDE/MALINDIALDEHYDE-ACETALDEHYDE ANTIBODIES PROMOTE OSTEOCLAST DEVELOPMENT ». Annals of the Rheumatic Diseases 80, Suppl 1 (19 mai 2021) : 429. http://dx.doi.org/10.1136/annrheumdis-2021-eular.3678.

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Background:Malondialdehyde (MDA) is a highly reactive compound generated during lipid-peroxidation in conditions associated with oxidative stress. MDA can irreversibly modify proteins (e.g. lysine, arginine and histidine residues). In addition, acetaldehyde can further react with MDA adducts to form malondialdehyde-acetaldehyde (MAA) modification. Such protein modifications can lead to immunogenic neo-epitopes that are recognized by autoantibodies. In fact, anti-MDA/MAA IgG antibodies are significantly increased in the serum of patients with autoimmune diseases, such as rheumatoid arthritis (RA) (1). Interestingly, anti-MDA/MAA antibodies have been shown to promote osteoclast (OC) differentiation in vitro suggesting a potential role for these autoantibodies in bone damage associated with RA (1).Objectives:Little is known about the molecular mechanisms activated by autoantibodies in RA. Here, we elucidate the pathways specifically triggered by anti-MDA/MAA autoantibodies in developing osteoclasts.Methods:Recombinant human monoclonal anti-MDA/MAA antibodies, which were previously cloned from single synovial B cells of RA patients, were added to different OC assays. OCs were generated from monocyte-derived macrophages in the presence of the cytokines RANK-L and M-CSF. OC development was monitored by light microscopy following tartrate-resistant acid phosphatase staining and by erosion assays using calcium phosphate-coated plates. Bone morphometrics were studied in anti-MDA/MAA-injected mice using X-ray microscopy. Cellular metabolism was analyzed by mass spectrometry, Seahorse XF Analyzer and a colorimetric L-Lactate assay.Results:Anti-MDA/MAA antibodies induced a robust OC differentiation in vitro and bone loss in vivo. The anti-MDA/MAA antibodies acted on developing OCs by increasing glycolysis via an Fcγ receptor I-mediated pathway and the upregulation of the transcription factors HIF-1α, Myc and CHREBP. Such regulation of cellular metabolism was exclusively observed in the presence of the osteoclastogenic anti-MDA/MAA clones, whereas other RA-associated autoantibodies (anti-MDA/MAA or anti-citrullinated protein antibodies) had no effect on metabolism. The anti-MDA/MAA treatment induced a shift in the tricarboxylic acid (TCA) cycle activity in developing OCs, leading to the accumulation of citrate and aconitate.Conclusion:We described a novel type of autoantibody-induced pathway in RA, which might contribute to increased OC activation and a consequent bone loss. Anti-MDA/MAA antibodies promoted osteoclast development by increasing glycolysis and by modulating the TCA cycle through a signaling pathway that included Fcγ receptor I and a network of transcription factors acting on glycolysis. A TCA cycle bias towards citrate production suggests that the anti-MDA/MAA antibodies might stimulate OCs via increasing lipid biosynthesis in the cells.References:[1]Grönwall C. et al. J. Autoimmunity 84 (2017): 29-45.Acknowledgements:This Project has received funding from FOREUM, Foundation for Research in Rheumatology, from the European Research Council (ERC) grant agreement CoG 2017 - 7722209_PREVENT RA, the EU/EFPIA Innovative Medicine Initiative grant agreement 777357_RTCure, the Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse and Knut and Alice Wallenberg Foundation.Disclosure of Interests:Koji Sakuraba: None declared, Akilan Krishnamurthy: None declared, Alexandra Circiumaru: None declared, Vijay Joshua: None declared, Heidi Wähämaa: None declared, Marianne Engström: None declared, Meng Sun: None declared, Xiaowei Zheng: None declared, Cheng Xu: None declared, Khaled Amara: None declared, Vivianne Malmström Grant/research support from: collaboration with Pfizer, unrelated to the abstract, Sergiu-Bogdan Catrina: None declared, Caroline Grönwall: None declared, Bence Réthi: None declared, Anca Catrina Grant/research support from: collaboration with BMS and Pfizer, unrelated to the present abstract

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Hsu, Yu-Cheng, I.-Jung Tsai, Hung Hsu, Po-Wen Hsu, Ming-Hui Cheng, Ying-Li Huang, Jin-Hua Chen, Meng-Huan Lei et Ching-Yu Lin. « Using Anti-Malondialdehyde Modified Peptide Autoantibodies to Import Machine Learning for Predicting Coronary Artery Stenosis in Taiwanese Patients with Coronary Artery Disease ». Diagnostics 11, n^o 6 (26 mai 2021) : 961. http://dx.doi.org/10.3390/diagnostics11060961.

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Machine learning (ML) algorithms have been applied to predicting coronary artery disease (CAD). Our purpose was to utilize autoantibody isotypes against four different unmodified and malondialdehyde (MDA)-modified peptides among Taiwanese with CAD and healthy controls (HCs) for CAD prediction. In this study, levels of MDA, MDA-modified protein (MDA-protein) adducts, and autoantibody isotypes against unmodified peptides and MDA-modified peptides were measured with enzyme-linked immunosorbent assay (ELISA). To improve the performance of ML, we used decision tree (DT), random forest (RF), and support vector machine (SVM) coupled with five-fold cross validation and parameters optimization. Levels of plasma MDA and MDA-protein adducts were higher in CAD patients than in HCs. IgM anti-IGKC76–99 MDA and IgM anti-A1AT284–298 MDA decreased the most in patients with CAD compared to HCs. In the experimental results of CAD prediction, the decision tree classifier achieved an area under the curve (AUC) of 0.81; the random forest classifier achieved an AUC of 0.94; the support vector machine achieved an AUC of 0.65 for differentiating between CAD patients with stenosis rates of 70% and HCs. In this study, we demonstrated that autoantibody isotypes imported into machine learning algorithms can lead to accurate models for clinical use.

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Malik, Rifkind, Rhandyka Rafli, Salmi Salmi et Yasinta Allisya Noer. « Relationship of Sleep Quality and Oxidative Stress Level in Smartphone Users ; Study in Faculty of Medicine Student, Universitas Baiturrahmah ». Open Access Macedonian Journal of Medical Sciences 10, B (21 février 2022) : 501–5. http://dx.doi.org/10.3889/oamjms.2022.8593.

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BACKGROUND: Excessive smartphones can affect sleep quality, reducing sleep duration. This lack of sleep will impact various health and increase levels of free radicals in the body, affecting various cell functions. AIM: The aim of the study was to measure the relationship between sleep quality due to smartphone use and serum malondialdehyde (MDA) levels. MATERIALS AND METHODS: This was a quasi-experimental with pre- and post-test group study. Sleep quality was assessed with Pittsburgh Sleep Quality Index (PSQI), and the smartphone addiction was assessed based on Smartphone Addiction Scale (SAS) score. The subjects were divided into four groups (n = 6) based on their PSQI and SAS score. The first group was the subjects with normal sleep and non-smartphone addict. The second group was the subjects with normal sleep but smartphone addict. The third group was the subjects with abnormal sleep and non-smartphone addict. Furthermore, fourth was the subjects with abnormal sleep and smartphone addiction. All the subjects were asked to sleep usually and used the smartphone as necessary a day before the study started. Blood plasma was collected from the subject before and after the study for MDA measurement. Plasma MDA was determined using the thiobarbituric acid test. RESULTS: Smartphone use can reduce sleep quality and duration, resulting in sleep deprivation. There was no increase in MDA concentration (p > 0.05) in the ordinary and non-addictive or smartphone-addicted sleep group. Meanwhile, the group that stayed up late and was neither addictive nor addictive showed an increase in MDA levels and was statistically significant (p < 0.05). CONCLUSION: Adequate sleep can reduce blood serum MDA levels and smartphone use does not affect MDA levels.

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Mène-Saffrané, Laurent, Céline Davoine, Stéphanie Stolz, Paul Majcherczyk et Edward E. Farmer. « Genetic Removal of Tri-unsaturated Fatty Acids Suppresses Developmental and Molecular Phenotypes of an Arabidopsis Tocopherol-deficient Mutant ». Journal of Biological Chemistry 282, n^o 49 (10 octobre 2007) : 35749–56. http://dx.doi.org/10.1074/jbc.m706838200.

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Malondialdehyde (MDA) is a small, ubiquitous, and potentially toxic aldehyde that is produced in vivo by lipid oxidation and that is able to affect gene expression. Tocopherol deficiency in the vitamin E2 mutant vte2-1 of Arabidopsis thaliana leads to massive lipid oxidation and MDA accumulation shortly after germination. MDA accumulation correlates with a strong visual phenotype (growth reduction, cotyledon bleaching) and aberrant GST1 (glutathione S-transferase 1) expression. We suppressed MDA accumulation in the vte2-1 background by genetically removing tri-unsaturated fatty acids. The resulting quadruple mutant, fad3-2 fad7-2 fad8 vte2-1, did not display the visual phenotype or the aberrant GST1 expression observed in vte2-1. Moreover, cotyledon bleaching in vte2-1 was chemically phenocopied by treatment of wild-type plants with MDA. These data suggest that products of tri-unsaturated fatty acid oxidation underlie the vte2-1 seedling phenotype, including cellular toxicity and gene regulation properties. Generation of the quadruple mutant facilitated the development of an in situ fluorescence assay based on the formation of adducts of MDA with 2-thiobarbituric acid at 37 °C. Specificity was verified by measuring pentafluorophenylhydrazine derivatives of MDA and by liquid chromatography analysis of MDA-2-thiobarbituric acid adducts. Potentially applicable to other organisms, this method allowed the localization of MDA pools throughout the body of Arabidopsis and revealed an undiscovered pool of the compound unlikely to be derived from trienoic fatty acids in the vicinity of the root tip quiescent center.

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Ormiston, Kate, Kirti Kaul, Neelam Shinde, Allen Zhang, Morgan Bauer, Hee Kyung Kim, Ramesh K. Ganju, Sarmila Majumder et Bhuvaneswari Ramaswamy. « Abstract 5814 : Lack of breast feeding may contribute to increased breast cancer risk by altering metabolism ». Cancer Research 82, n^o 12_Supplement (15 juin 2022) : 5814. http://dx.doi.org/10.1158/1538-7445.am2022-5814.

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Abstract Purpose: Epidemiological data links lack of breastfeeding with increased risk of breast cancer, particularly triple negative breast cancer (TNBC). The involution process is characterized by mammary tissue remodeling, including adipocyte repopulation and re-differentiation fueled by metabolic rewiring. Our mouse model mimicking short-term breast feeding that leads to abrupt involution (AI) revealed a chronic inflammatory state in the mammary gland (MG) (Basree, et al. Breast Cancer Research; 2019). As metabolic dysfunction is linked to increased BC risk, we sought to elucidate the effects of AI and gradual involution (GI) on MG energy metabolism and associated oxidative stress. In addition, we evaluated the impact of AI and GI on whole body glucose metabolism and insulin response/resistance. Methods: FVB/n mice (8week old) were paired for breeding. At partum, dams were randomized to AI or GI cohort and standardized to 6 pups per dam. AI mice had pups removed on postpartum day 7 (d7) to mimic short-term breastfeeding. GI mice had 3 pups removed on day 28 and 31 each to mimic gradual weaning. MGs were harvested on d28, 56, and 120 postpartum. Prior to harvest, mice underwent an echoMRI and insulin tolerance test (ITT). At harvest, mice were fasted for 4 hours, and blood was collected for serum insulin measurement using Ultra-Sensitive Insulin ELISA. Lipid peroxidation (MDA) and DNA adduct formation (8-OHdG), which represent chronic oxidative stress, were measured in MG by ELISA. Whole MG RNA were subjected to affymetrix followed by gene set enrichment analyses (GSEA) and qPCR for target validation. MGs were also subjected to untargeted metabolomics analysis and Mitofuel flex assay to assess substrate dependence by Seahorse Bioanalyzer. Results: GSEA and qPCR revealed enrichment of fatty acid oxidation (FAO) and mitochondrial oxidative phosphorylation (OXPHOS) pathways in AI MGs at d28, further validated by expression of genes (PGC-1α, Cpt-2, Srebp1c, and Chrebp). Metabolites associated with FAO were enriched in AI MGs at d28 and 56. Mitofuel flex assay indicated a significantly higher dependence on FAO in AI MGs. On d56, fasted blood glucose was significantly higher in AI mice with serum insulin and HOMA-IR trending to be higher than in GI mice. Level of 8-OHdG was elevated in AI MGs at d120. AI mice trended to be heavier, have greater body fat, and lower lean mass than GI Mice at d120. Body weight and percent body fat on d120 were positively correlated to MDA concentration in the mammary gland. Conclusion: Our mouse models of AI and GI revealed early MG specific metabolic shift towards increased FAO and OXPHOS that persists over time in AI glands. Similarly, increased oxidative stress and its association with adiposity at d120 indicates continued effect of AI. This change in adiposity, altered systemic glucose metabolism and metabolic shift seen in AI mice may contribute to the higher risk of breast cancer. [K.O. and K.K. are co-first authors.] Citation Format: Kate Ormiston, Kirti Kaul, Neelam Shinde, Allen Zhang, Morgan Bauer, Hee Kyung Kim, Ramesh K. Ganju, Sarmila Majumder, Bhuvaneswari Ramaswamy. Lack of breast feeding may contribute to increased breast cancer risk by altering metabolism [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5814.

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Pathe, Gulab Khushalrao, Naveen K. Konduru, Iram Parveen et Naseem Ahmed. « Anti-proliferative activities of flavone–estradiol Stille-coupling adducts and of indanone-based compounds obtained by SnCl4/Zn-catalysed McMurry cross-coupling reactions ». RSC Advances 5, n^o 101 (2015) : 83512–21. http://dx.doi.org/10.1039/c5ra15685h.

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Flavone–estradiol adducts and indanophen based tamoxifen analogs are synthesized using SnCl₄–Zn reagent via McMurry reaction and evaluated in human cervical (HeLa) and breast cancer cells (MCF-7 and MDA-MB-231) for the anti-proliferative activity.

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Kaur, Sumeet, Satinder Pal Singh et Uma Gujral. « Role of Malondialdehyde (MDA) in senile cataract ». Journal of Medical Research 2, n^o 2 (25 avril 2016) : 44–46. http://dx.doi.org/10.31254/jmr.2016.2208.

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Cataract is characterized partial or complete loss of transparency of the lens that leads to loss of vision. Globally, cataract associated blindness is a major cause of morbidity in developing countries. The cataractogenesis is affected by a number of factors with redox imbalance at the top of list. This imbalance results either from an increased generation of free radicals and/or decreased production of antioxidants. The end products of lipid peroxidation are both mutagenic and carcinogenic. One such product, malondialdehyde (MDA) reacts with deoxyadenosine and deoxyguanosine in DNA, to form DNA adducts. Its role in cataractogenesis is due to its cross linking ability. The present study analyzed the role of MDA in the development of senile cataract. Its level was measured in 75 randomly selected senile cataract patients of different age groups and matched against suitable controls. The study found statistically significant increased levels of MDA in cataract patients but not in controls, indicating an oxidative stress. The present study concluded that increased levels of MDA increased the susceptibility to cataractogenesis.

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Poston, Robin N., Jenna Chughtai, Desara Ujkaj, Huguette Louis, David S. Leake et Dianne Cooper. « Monocytic Cell Adhesion to Oxidised Ligands : Relevance to Cardiovascular Disease ». Biomedicines 10, n^o 12 (30 novembre 2022) : 3083. http://dx.doi.org/10.3390/biomedicines10123083.

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Atherosclerosis, the major cause of vascular disease, is an inflammatory process driven by entry of blood monocytes into the arterial wall. LDL normally enters the wall, and stimulates monocyte adhesion by forming oxidation products such as oxidised phospholipids (oxPLs) and malondialdehyde. Adhesion molecules that bind monocytes to the wall permit traffic of these cells. CD14 is a monocyte surface receptor, a cofactor with TLR4 forming a complex that binds oxidised phospholipids and induces inflammatory changes in the cells, but data have been limited for monocyte adhesion. Here, we show that under static conditions, CD14 and TLR4 are implicated in adhesion of monocytes to solid phase oxidised LDL (oxLDL), and also that oxPL and malondialdehyde (MDA) adducts are involved in adhesion to oxLDL. Similarly, monocytes bound to heat shock protein 60 (HSP60), but this could be through contaminating lipopolysaccharide. Immunohistochemistry on atherosclerotic human arteries demonstrated increased endothelial MDA adducts and HSP60, but endothelial oxPL was not detected. We propose that monocytes could bind to MDA in endothelial cells, inducing atherosclerosis. Monocytes and platelets synergized in binding to oxLDL, forming aggregates; if this occurs at the arterial surface, they could precipitate thrombosis. These interactions could be targeted by cyclodextrins and oxidised phospholipid analogues for therapy.

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Shishodia, Shifali, et Christopher J. Schofield. « Improved Synthesis of Phosphoramidite-Protected N6-Methyladenosine via BOP-Mediated SNAr Reaction ». Molecules 26, n^o 1 (31 décembre 2020) : 147. http://dx.doi.org/10.3390/molecules26010147.

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N6-methyladenosine(m6A) is the most abundant modification in mRNA. Studies on proteins that introduce and bind m6A require the efficient synthesis of oligonucleotides containing m6A. We report an improved five-step synthesis of the m6A phosphoramidite starting from inosine, utilising a 1-H-benzotriazol-1-yloxytris(dimethylamino)phosphoniumhexafluorophosphate (BOP)-mediated SNAr reaction in the key step. The route manifests a substantial increase in overall yield compared to reported routes, and is useful for the synthesis of phosphoramidites of other adenosine derivatives, such as ethanoadenosine, an RNA analogue of the DNA adduct formed by the important anticancer drug Carmustine.

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Jiang, Yi Hua, Xin Long Jiang et Shun Tang. « Copigmentation of Mahonia Bealei Anthocyanins by Tannin ». Advanced Materials Research 726-731 (août 2013) : 523–29. http://dx.doi.org/10.4028/www.scientific.net/amr.726-731.523.

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This study investigates the copigmentation effect and its underlying mechanism of tannin on Mahonia bealei anthocyanins (MBA). Results show that the addition of tannin increases the absorption and maximum absorption wavelength of MBA. At pH 3.73, the activation energy of MBA-tannin adduct is 2.43 times that of MBA. Under the same temperature, MBA-tannin complex shows better heat stability as exemplified by lower degradation rate and longer half-time. The light-induced degradation rate constant of MBA-tannin is 93.33% of that of MBA. It is shown in this paper that tannin can improve the heat and light stability of MBA and therefore is efficient as a copigment. Finally, the IR spectra suggest that the copigmentation effect is due to the formation of hydrogen bonds between tannin and MBA via associated hydroxyl groups.

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Pérez-Peiró, Maria, Clara Martín-Ontiyuelo, Anna Rodó-Pi, Lucilla Piccari, Mireia Admetlló, Xavier Durán, Diego A. Rodríguez-Chiaradía et Esther Barreiro. « Iron Replacement and Redox Balance in Non-Anemic and Mildly Anemic Iron Deficiency COPD Patients : Insights from a Clinical Trial ». Biomedicines 9, n^o 9 (10 septembre 2021) : 1191. http://dx.doi.org/10.3390/biomedicines9091191.

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In COPD patients, non-anemic iron deficiency (NAID) is a common systemic manifestation. We hypothesized that in COPD patients with NAID, iron therapy may improve systemic oxidative stress. The FACE (Ferinject assessment in patients with COPD and iron deficiency to improve exercise tolerance) study was a single-blind, unicentric, parallel-group, placebo-controlled clinical trial (trial registry: 2016-001238-89). Sixty-six patients were enrolled (randomization 2:1): iron arm, n = 44 and placebo arm, n = 22, with similar clinical characteristics. Serum levels of 3-nitrotyrosine, MDA-protein adducts, and reactive carbonyls, catalase, superoxide dismutase (SOD), glutathione, Trolox equivalent antioxidant capacity (TEAC), and iron metabolism biomarkers were quantified in both groups. In the iron-treated patients compared to placebo, MDA-protein adducts and 3-nitrotyrosine serum levels significantly declined, while those of GSH increased and iron metabolism parameters significantly improved. Hepcidin was associated with iron status parameters. This randomized clinical trial evidenced that iron replacement elicited a decline in serum oxidative stress markers along with an improvement in GSH levels in patients with stable severe COPD. Hepcidin may be a surrogate biomarker of iron status and metabolism in patients with chronic respiratory diseases. These findings have potential clinical implications in the management of patients with severe COPD.

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Clemens, Dahn, Michael Duryee, Cleofes Sarmiento, Andrew Chiou, Jacob McGowan, Carlos Hunter, Sarah Schlichte et al. « Novel Antioxidant Properties of Doxycycline ». International Journal of Molecular Sciences 19, n^o 12 (17 décembre 2018) : 4078. http://dx.doi.org/10.3390/ijms19124078.

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Doxycycline (DOX), a derivative of tetracycline, is a broad-spectrum antibiotic that exhibits a number of therapeutic activities in addition to its antibacterial properties. For example, DOX has been used in the management of a number of diseases characterized by chronic inflammation. One potential mechanism by which DOX inhibits the progression of these diseases is by reducing oxidative stress, thereby inhibiting subsequent lipid peroxidation and inflammatory responses. Herein, we tested the hypothesis that DOX directly scavenges reactive oxygen species (ROS) and inhibits the formation of redox-mediated malondialdehyde-acetaldehyde (MAA) protein adducts. Using a cell-free system, we demonstrated that DOX scavenged reactive oxygen species (ROS) produced during the formation of MAA-adducts and inhibits the formation of MAA-protein adducts. To determine whether DOX scavenges specific ROS, we examined the ability of DOX to directly scavenge superoxide and hydrogen peroxide. Using electron paramagnetic resonance (EPR) spectroscopy, we found that DOX directly scavenged superoxide, but not hydrogen peroxide. Additionally, we found that DOX inhibits MAA-induced activation of Nrf2, a redox-sensitive transcription factor. Together, these findings demonstrate the under-recognized direct antioxidant property of DOX that may help to explain its therapeutic potential in the treatment of conditions characterized by chronic inflammation and increased oxidative stress.

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Meguellati, Kamel, Martin Spichty et Sylvain Ladame. « Synthesis, spectroscopic and DNA alkylating properties of malondialdehyde (MDA) bis-imine fluorescent adducts ». Molecular BioSystems 6, n^o 9 (2010) : 1694. http://dx.doi.org/10.1039/c002157a.

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Tatzber, Franz, Edith Pursch, Ulrike Resch, Roswitha Pfragner, Sandra Holasek, Meinrad Lindschinger, Gerhard Cvirn et Willibald Wonisch. « Cultivation and Immortalization of Human B-Cells Producing a Human Monoclonal IgM Antibody Binding to MDA-LDL : Further Evidence for Formation of Atherogenic MDA-LDL Adducts in HumansIn Vivo ». Oxidative Medicine and Cellular Longevity 2017 (2017) : 1–7. http://dx.doi.org/10.1155/2017/6047142.

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Oxidatively modified low-density lipoprotein (oLDL) is firmly believed to play an important role in the initiation and development of atherosclerosis, and malonic dialdehyde (MDA) is one of the major lipid peroxidation breakdown products involved in this process. In recent decades, antibodies against MDA-LDL have been detected in human and animal sera. In our study, human B-cells from the peripheral blood of a healthy female donor were fused with the SP2/0 mouse myeloma cell line. Antibody-producing hybridomas were detected by MDA-LDL-IgG/IgM enzyme-linked immunosorbent assays (ELISA) and Cu++-oxidized LDL IgG/IgM (oLAb) ELISA. Cells with supernatants emitting positive signals for antibodies were then cloned and after sufficient multiplication frozen and stored under liquid nitrogen. Due to the loss of antibody-producing ability, we established an MDA-LDL-IgM-producing cell line by recloning. This allowed isolation and immortalization of several human B-cells. The human donor had not been immunized with MDA-modified proteins, thus obviously producing MDA-LDL antibodiesin vivo. Furthermore, using these antibodies forin vitroexperiments, we were able to demonstrate that MDA epitopes are among the epitopes generated during Cu++-LDL oxidation as well. Finally, these antibodies compete in ELISA and cell culture experiments with MDA as a challenging toxin or ligand.

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Thai, Sheau-Fung, Carlton P. Jones, Garret B. Nelson, Beena Vallanat, Micaela Killius, James L. Crooks, William O. Ward, Carl F. Blackman et Jeffrey A. Ross. « Differential Effects of Nano TiO2 and CeO2 on Normal Human Lung Epithelial Cells In Vitro ». Journal of Nanoscience and Nanotechnology 19, n^o 11 (1 novembre 2019) : 6907–23. http://dx.doi.org/10.1166/jnn.2019.16737.

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Nano-TiO2 and nano-CeO2 are among the most widely used engineered nanoparticles (NPs). We investigated a variety of endpoints to assess the toxicity of eight of these NPs to induce potentially adverse health effects in an In Vitro human respiratory epithelial cell model. These endpoints include cytotoxicity, reactive oxygen species (ROS)/reactive nitrogen species (RNS) production, 8-hydroxy-2_-deoxyguanosine (8-oxo-dG), endogenous DNA adducts, Apurinic/apyrimidinic (AP) sites, 4-Hrdoxynonenal (4-HNE) protein adducts, Malondialdehyde (MDA) protein adducts, and genomics analysis on altered signaling pathways. Our results indicated that cytotoxicity assays are relatively insensitive, and we detected changes in other endpoints at concentrations much lower than those inducing cytotoxicity. Among the ROS-related endpoints, 8-oxo-dG is relatively more sensitive than other assays, and nano-TiO2 induced more 8-oxo-dG formation than nano-CeO2. Finally, there are many signaling pathways changes at concentrations at which no cytotoxicity was observed. These alterations in signaling pathways correlated well with In Vitro toxicity that was observed at higher concentrations, and with in vivo adverse outcome pathways caused by nano-TiO2 and nano-CeO2 in experimental animals.

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Valerio Jr, Luis G., et Dennis R. Petersen. « Formation of liver microsomal MDA–protein adducts in mice with chronic dietary iron overload ». Toxicology Letters 98, n^o 1-2 (septembre 1998) : 31–39. http://dx.doi.org/10.1016/s0378-4274(98)00100-3.

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Kim, Daejung, Dai-Soo Lee et Youn-Sik Lee. « Curing Behavior of an Epoxy Resin with Hardener Formulations Composed of MDI-phenol Adduct and Diethylenetriamine ». Polymer Korea 42, n^o 1 (31 janvier 2018) : 1–7. http://dx.doi.org/10.7317/pk.2018.42.1.1.

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Atalay, Sinemyiz, Agnieszka Gęgotek et Elżbieta Skrzydlewska. « Protective Effects of Cannabidiol on the Membrane Proteome of UVB-Irradiated Keratinocytes ». Antioxidants 10, n^o 3 (8 mars 2021) : 402. http://dx.doi.org/10.3390/antiox10030402.

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Ultraviolet (UV) radiation contained in sunlight disturbs the redox state of skin cells, leading to changes in the structures and functions of macromolecules including components of biological membranes. Cannabidiol (CBD), which accumulates in biomembranes, may be a promising protective antioxidant compound. Accordingly, the aim of this study was to compare the effects of short-term (24 h) and long-term (48 h) CBD application on the proteomic profile of biological membranes in UVB-irradiated keratinocytes. The data obtained show that UVB radiation quantitatively and qualitatively modified cell membrane proteins, with a particular research focus on adducts of proteins with the lipid peroxidation products malondialdehyde (MDA) or 4-hydroxynonenal (4-HNE). CBD application reduced the UVB-enhanced level of these protein adducts. This was particularly notable amongst proteins related to cell proliferation and apoptosis. Moreover, CBD dramatically increased the UVB-induced expression of proteins involved in the regulation of protein translation and cell proliferation (S3a/L13a/L7a ribosomal proteins), the inflammatory response (S100/S100-A6 proteins), and maintenance of redox balance (peroxiredoxin-1, carbonyl reductase 1, and aldo-keto reductase family 1 members). In contrast, CBD effects on the level of 4-HNE-protein adducts involved in the antioxidant response and proteasomal degradation process indicate that CBD may protect keratinocytes in connection with protein catabolism processes or pro-apoptotic action.

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GREILBERGER, Joachim, et Günther JÜRGENS. « Oxidation of high-density lipoprotein HDL3 leads to exposure of apo-AI and apo-AII epitopes and to formation of aldehyde protein adducts, and influences binding of oxidized low-density lipoprotein to type I and type III collagen in vitro1 ». Biochemical Journal 331, n^o 1 (1 avril 1998) : 185–91. http://dx.doi.org/10.1042/bj3310185.

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The changes in the immunological properties of apolipoprotein AI (apo-AI) and AII (apo-AII) during the oxidation of the high-density lipoprotein HDL3 and its influence on the binding of heavily oxidized low-density lipoprotein (LDL) to type I and III collagen were investigated. Oxidation of HDL3 or Eu3+-labelled HDL3 was performed with CuSO4, varying the time of oxidation. Oxidation of HDL3 resulted in an increase in lipid hydroperoxides and enhanced the negative charge of this lipoprotein. Immunological studies with a solid-phase sandwich immunoassay revealed a strong increase in binding of Eu3+-labelled HDL3 to polyclonal antibodies against apo-AI and apo-AII within the first 4 h of oxidation. Neo-epitopes were also formed by interaction of the apolipoproteins with degradation products from the lipid peroxidation of polyunsaturated fatty acids, as evidenced by an immunoreaction of oxidized Eu3+-labelled HDL3 with antibodies to 4-hydroxynonenal (4-HNE)– and malondialdehyde (MDA)–protein adducts. Western blot analysis of oxidized HDL3 samples showed, as well as apo-AI and apo-AII bands, larger aggregated apolipoproteins, occurring after 0.5–2.5 h of oxidation. These aggregates were recognized by antibodies to apo-AI and apo-AII as well as by antibodies to 4-HNE- and MDA-protein adducts. Furthermore the original apo-AI monomers and apo-AII dimers decreased during the oxidation. The ability of native and oxidized HDL3 to prevent the binding of Eu3+-labelled 24 h-oxidized LDL to collagen on microtitration plates was estimated. Interestingly, 2 h-oxidized HDL3 competed most with the binding of 24 h-oxidized LDL on collagen type I and type III, followed by native HDL3. However, 24 h-oxidized HDL3 was a weaker competitor. Thus oxidative modification of HDL3 strongly alters the immunological properties of this lipoprotein and its binding affinity for collagen.

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Ramirez, Jessica, Elizabeth Paris, Sanjib Basu et Animesh Barua. « Abstract A015 : Age-associated molecular changes may predispose the ovary to malignant transformation leading to ovarian cancer (OVCA) ». Cancer Research 83, n^o 2_Supplement_1 (15 janvier 2023) : A015. http://dx.doi.org/10.1158/1538-7445.agca22-a015.

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Abstract Background: Ovarian cancer (OVCA) is a fatal malignancy of women which in most cases is a disease of postmenopausal women. Thus, age-associated changes in women may predispose them to malignancy. Persistent high levels of follicle stimulating hormone (FSH) is a feature of aging and we have shown that aging was associated with increased expression of inflammatory cytokine interleukin 16 (IL-16) and glucose regulatory protein (GRP78), a marker of cellular stress. It is possible that age-associated increased expression of IL-16 and GRP78 might be involved in production of mutagenic 8-OXO-2dG or its cognate enzyme OGG1 and malondialdehyde (MDA) as well as markers of DNA repair mechanisms. The goal of this study was to determine the mechanism of age-associated malignant transformation in the ovary. Materials and Methods: Exploratory study: Archived tissue specimens were selected for immunohistochemical, immunoblotting, genomic studies and immunoassays based on the review of their hematoxylin and eosin staining and final Pathological reports. Specimens were grouped as normal premenopausal women (30-50 years old), normal postmenopausal women (55-85 years old) and ovarian high grade serous carcinoma (HGSC). In vitro study: human ovarian surface epithelium (HOSE) cells were treated with or without FSH for 24 hours, and their cytoplasmic and nuclear fractionations together with that of OVCAR3 (HGSC cell line) cells were extracted. Expression of markers of inflammation (IL-16), oxidative stress (SOD2, GRP78), DNA adducts (8-OXO-2dG/OGG1, MDA) and epigenetics (HDAC1, gH2AX) and were examined. Significant differences in expression of different markers among different age groups and ovarian HGSC, and treated or control OVCAR3 cells were determined by ANOVA and t-tests. Results: Compared with premenopausal women, expression of markers of inflammation and oxidative stress including IL-16, GRP78, SOD2, 8-OXO-2dG/OGG1, MDA as well as markers of epigenetic changes including HDAC1 and gH2AX was significantly higher (<0.0001) in a subset of postmenopausal women. Similar patterns of expression were also observed in patients with ovarian HGSC. Nuclear expression of mutagenic DNA adducts (OGG1, MDA) and inhibitor of DNA damage repair mechanism (GRP78) enhanced during aging. Thus, age-associated inflammation and oxidative stress are predispositions to malignant transformation. This assumption is based on the observation from the treatment of HOSE cells with FSH which showed increased expression of the above markers as also observed in OVCAR3 cells. Conclusion: Expression of IL-16, GRP78, SOD2, 8-OXO-2dG/OGG1, MDA and HDAC1 increased in ovary during aging. These results suggest that aging is associated with persistent inflammation and oxidative stress in ovarian tissues, which predisposes these tissues to malignant transformation leading to OVCA development. Support: NIH/NCI: CA210370 Citation Format: Jessica Ramirez, Elizabeth Paris, Sanjib Basu, Animesh Barua. Age-associated molecular changes may predispose the ovary to malignant transformation leading to ovarian cancer (OVCA) [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A015.

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Upur, Halmurat, Abdiryim Yusup, Isabelle Baudrimont, Anwar Umar, Benedicte Berke, Dilxat Yimit, Jaya Conser Lapham, Edmon E. Creppy et Nicholas Moore. « Inhibition of Cell Growth and Cellular Protein, DNA and RNA Synthesis in Human Hepatoma (HepG2) Cells by Ethanol Extract of Abnormal Savda Munziq of Traditional Uighur Medicine ». Evidence-Based Complementary and Alternative Medicine 2011 (2011) : 1–9. http://dx.doi.org/10.1093/ecam/nen062.

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Abnormal Savda Munziq (ASMq) is a traditional Uighur medicinal herbal preparation, commonly used for the treatment and prevention of cancer. We tested the effects of ethanol extract of ASMq on cultured human hepatoma cells (HepG2) to explore the mechanism of its putative anticancer properties, using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) bromide, neutral red and lactate dehydrogenase (LDH) leakage assays, testing the incorporation of3[H]-leucine and3[H]-nucleosides into protein, DNA and RNA, and quantifying the formation of malondialdehyde-thiobarbituric acid (MDA) adducts. ASMq ethanol extract significantly inhibited the growth of HepG2 and cell viability, increased the leakage of LDH after 48 hours or 72 hours treatment, in a concentration- and time-dependent manner (P< .05). Cellular protein, DNA and RNA synthesis were inhibited in a concentration- and time-dependent manner (P< .05). No significant MDA release in culture medium and no lipid peroxidation in cells were observed. The results suggest that the cytotoxic effects of ASMq ethanol extract might be related to inhibition of cancer cell growth, alteration of cell membrane integrity and inhibition of cellular protein, DNA and RNA synthesis.

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Papac-Milicevic, Nikolina, Lejla Alic, Darina Czamara, Michael Gurbisz, Maria Ozsvar-Kozma, Stefanie Haslinger-Hutter, Gregor Hoermann et al. « A genome-wide association study identifies FHR1 and FHR3 as competitors for FH binding to MDA-adducts ». Molecular Immunology 102 (octobre 2018) : 195–96. http://dx.doi.org/10.1016/j.molimm.2018.06.172.

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